Low LATS2 mRNA level can predict favorable response to epirubicin plus cyclophosphamide, but not to docetaxel, in breast cancers

Abstract

Putative tumor suppressor genes LATS1 and LATS2 are implicated in the regulation of the cell cycle at the G2/M and G1/S phase, respectively. This study investigated possible correlations of intra-tumoral LATS1 and LATS2 mRNA levels with response to epirubicin plus cyclophosphamide (EC) or docetaxel (DOC) treatment. mRNA expression levels of LATS1 and LATS2 were determined by means of real-time PCR assay in 56 locally advanced breast cancers and 15 recurrent breast cancers treated with EC (n = 32) or DOC (n = 39). Among the patients treated with EC, LATS2 mRNA levels of responders (0.72 ± 0.11, mean ± SE) were significantly (P < 0.05) lower than those of non-responders (1.62 ± 0.44), and responders showed a tendency (P = 0.05) towards reduced LATS1 mRNA levels. Patients with low LATS2 mRNA levels (n = 16) showed a significantly (P < 0.05) higher response rate (75%) to EC treatment than those with high LATS2 mRNA levels (n = 16; response rate = 31%). Positive predictive value, negative predictive value, and diagnostic accuracy of LATS2 mRNA levels for prediction of response to EC were 75, 69, and 72%, respectively. On the other hand, neither LATS1 nor LATS2 mRNA levels were associated with response to DOC treatment. These results suggest the possibility that intra-tumoral LATS2 mRNA levels may be clinically useful for the prediction of response to EC treatment by breast cancer patients. We speculate that disruption of the checkpoint function at the G1/S phase induced by down-regulation of LATS2 plays some part in the favorable response to EC.